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Janus kinase 2

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Target id: 2048

Nomenclature: Janus kinase 2

Abbreviated Name: JAK2

Family: Janus kinase (JakA) family

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 1132 9p24.1 JAK2 Janus kinase 2
Mouse - 1129 19 23.73 cM Jak2 Janus kinase 2
Rat - 1132 1q52 Jak2 Janus kinase 2
Previous and Unofficial Names Click here for help
JTK10
Database Links Click here for help
Alphafold O60674 (Hs), Q62120 (Mm), Q62689 (Rn)
BRENDA 2.7.10.2
CATH/Gene3D 1.20.80.10, 3.30.505.10
ChEMBL Target CHEMBL2971 (Hs), CHEMBL1649049 (Mm), CHEMBL1075225 (Rn)
DrugBank Target O60674 (Hs)
Ensembl Gene ENSG00000096968 (Hs), ENSMUSG00000024789 (Mm), ENSRNOG00000059968 (Rn)
Entrez Gene 3717 (Hs), 16452 (Mm), 24514 (Rn)
Human Protein Atlas ENSG00000096968 (Hs)
KEGG Enzyme 2.7.10.2
KEGG Gene hsa:3717 (Hs), mmu:16452 (Mm), rno:24514 (Rn)
OMIM 147796 (Hs)
Orphanet ORPHA122727 (Hs)
Pharos O60674 (Hs)
RefSeq Nucleotide NM_004972 (Hs), NM_001048177 (Mm), NM_031514 (Rn)
RefSeq Protein NP_004963 (Hs), NP_001041642 (Mm), NP_113702 (Rn)
SynPHARM 80886 (in complex with BMS-911543)
81944 (in complex with decernotinib)
85295 (in complex with decernotinib)
85292 (in complex with filgotinib)
80797 (in complex with filgotinib)
80436 (in complex with JAK inhibitor I)
85312 (in complex with JNJ-7706621)
85286 (in complex with PF-04965842)
85309 (in complex with PF-06263276)
85282 (in complex with tofacitinib)
UniProtKB O60674 (Hs), Q62120 (Mm), Q62689 (Rn)
Wikipedia JAK2 (Hs)
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Structural basis of Jak2 inhibition by the type II inhibtor NVP-BBT594
PDB Id:  3UGC
Ligand:  NVP-BBT594
Resolution:  1.34Å
Species:  Human
References:  2
Image of receptor 3D structure from RCSB PDB
Description:  Crystal Structure of JAK2 in complex with compound 25
PDB Id:  6BBV
Ligand:  abrocitinib
Resolution:  1.8Å
Species:  Human
References:  72
Image of receptor 3D structure from RCSB PDB
Description:  Discovery of 1-Methyl-1H-imidazole Derivatives as Potent Jak2 Inhibitors
PDB Id:  4C61
Ligand:  compound 19a [PMID: 24359159]
Resolution:  2.45Å
Species:  Human
References:  66
Image of receptor 3D structure from RCSB PDB
Description:  The structural basis of Janus Kinase 2 inhibition by a potent and specific pan-Janus kinase inhibitor (pyridone 6)
PDB Id:  2B7A
Ligand:  JAK inhibitor I
Resolution:  2.0Å
Species:  Human
References:  49
Enzyme Reaction Click here for help
EC Number: 2.7.10.2

Download all structure-activity data for this target as a CSV file go icon to follow link

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
RG-1530 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.5 pKd 70
⤷ pKd 7.5 (Kd 2.9x10-8 M) [70]
JNJ-7706621 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Binding 6.3 pKd 47,58
⤷ pKd 6.3 (Kd 4.56x10-7 M) [47]
Description: Affinity for JAK2 JH2 by competitive fluorescence polarization (FP) assay
pKd 6.3 (Kd 4.6x10-7 M) [58]
Description: Binding affinity for JAK2 JH2 pseudokinase domain
BIIB068 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 6.3 pKd 50
⤷ pKd 6.3 (Kd 4.6x10-7 M) [50]
compound 13 [PMID: 35653642] Small molecule or natural product Hs Binding 5.2 – 7.5 pKd 47
⤷ pKd 7.5 (Kd 3.34x10-8 M) [47]
Description: Binding affinity for JAK2 JH2 wild-type
pKd 5.2 (Kd 6.81x10-6 M) [47]
Description: Binding affinity for JAK2 JH1
compound 11 [PMID: 35653642] Small molecule or natural product Ligand has a PDB structure Hs Binding 5.5 – 7.1 pKd 47
⤷ pKd 7.1 (Kd 7.5x10-8 M) [47]
Description: Binding affinity for JAK2 JH2 wild-type
pKd 5.5 (Kd 3.36x10-6 M) [47]
Description: Binding affinity for JAK2 JH1 (active kinase domain)
nezulcitinib Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 10.5 pKi 48
⤷ pKi 10.5 (Ki 3.1x10-11 M) [48]
izencitinib Small molecule or natural product Primary target of this compound Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition >10.0 pKi 36
⤷ pKi >10.0 (Ki <1x10-10 M) [36]
AZ960 Small molecule or natural product Primary target of this compound Hs Inhibition 9.4 pKi 30
⤷ pKi 9.4 (Ki 4.5x10-10 M) [30]
GDC-0214 Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 9.2 pKi 20
⤷ pKi 9.2 (Ki 6.2x10-10 M) [20]
delgocitinib Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 8.8 pKi 67
⤷ pKi 8.8 (Ki 1.7x10-9 M) [67]
Description: In an assay using the kinase domain of the recombinant human enzyme, a biotinylated peptide substrate, and [33P]ATP.
HG-10-102-01 Small molecule or natural product Click here for species-specific activity table Hs Inhibition <5.5 pKi 15
⤷ pKi <5.5 (Ki >3.2x10-6 M) [15]
compound 18e [PMID: 31670517] Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 9.1 pIC50 86
⤷ pIC50 9.1 (IC50 7x10-10 M) [86]
ilginatinib Small molecule or natural product Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 9.1 pIC50 54
⤷ pIC50 9.1 (IC50 7.2x10-10 M) [54]
tinengotinib Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 9.1 pIC50 83
⤷ pIC50 9.1 (IC50 7.5x10-10 M) [83]
JAK inhibitor I Small molecule or natural product Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 9.0 pIC50 69
⤷ pIC50 9.0 (IC50 1x10-9 M) [69]
BMS-911543 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 9.0 pIC50 59
⤷ pIC50 9.0 (IC50 1x10-9 M) [59]
compound 1d [PMID: 21493067] Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition >9.0 pIC50 77
⤷ pIC50 >9.0 (IC50 <1x10-9 M) [77]
repotrectinib Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 9.0 pIC50 21
⤷ pIC50 9.0 (IC50 1.04x10-9 M) [21]
AT-9283 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 8.9 pIC50 34
⤷ pIC50 8.9 (IC50 1.2x10-9 M) [34]
ruxolitinib Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 8.1 – 9.6 pIC50 17,32,61
⤷ pIC50 8.6 – 9.6 (IC50 2.8x10-9 – 2.4x10-10 M) [32,61]
pIC50 8.1 (IC50 9x10-9 M) [17]
LASW1393 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 8.8 pIC50 4
⤷ pIC50 8.8 (IC50 1.5x10-9 M) [4]
CEP-33779 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 8.7 pIC50 22
⤷ pIC50 8.7 (IC50 1.8x10-9 M) [22]
compound 25ap [PMID: 37796543] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.7 pIC50 90
⤷ pIC50 8.7 (IC50 1.8x10-9 M) [90]
XL019 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 8.7 pIC50 25
⤷ pIC50 8.7 (IC50 2.2x10-9 M) [25]
delgocitinib Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 8.6 pIC50 56
⤷ pIC50 8.6 (IC50 2.6x10-9 M) [56]
fedratinib Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.5 pIC50 52,78
⤷ pIC50 8.5 (IC50 3x10-9 M) [52,78]
compound 19a [PMID: 24359159] Small molecule or natural product Click here for species-specific activity table Hs Inhibition >8.5 pIC50 66
⤷ pIC50 >8.5 (IC50 <3x10-9 M) [66]
compound 13ac [PMID: 33256400] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.5 pIC50 85
⤷ pIC50 8.5 (IC50 3x10-9 M) [85]
Description: Inhibitory effect in a biochemical enzyme assay
JAK inhibitor 17b Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 8.4 pIC50 23
⤷ pIC50 8.4 (IC50 3.57x10-9 M) [23]
gandotinib Small molecule or natural product Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 8.4 pIC50 51
⤷ pIC50 8.4 (IC50 4x10-9 M) [51]
peficitinib Small molecule or natural product Approved drug Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 8.3 pIC50 37
⤷ pIC50 8.3 (IC50 5x10-9 M) [37]
ivarmacitinib Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 8.3 pIC50 89
⤷ pIC50 8.3 (IC50 5x10-9 M) [89]
momelotinib Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.7 – 8.9 pIC50 3,57
⤷ pIC50 8.9 (IC50 1.4x10-9 M) [3]
pIC50 7.7 (IC50 1.8x10-8 M) [57]
cerdulatinib Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 8.2 pIC50 18
⤷ pIC50 8.2 (IC50 6x10-9 M) [18]
baricitinib Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 8.1 – 8.2 pIC50 17,26
⤷ pIC50 8.2 (IC50 5.7x10-9 M) [26]
pIC50 8.1 (IC50 7x10-9 M) [17]
PF-956980 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.1 pIC50 31
⤷ pIC50 8.1 (IC50 7.1x10-9 M) [31]
AZD1480 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.1 pIC50 30
⤷ pIC50 8.1 (IC50 8x10-9 M) [30]
compound 30 [PMID: 37057760] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.1 pIC50 60
⤷ pIC50 8.1 (IC50 8.36x10-9 M) [60]
lorpucitinib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 8.1 pIC50 40
⤷ pIC50 8.1 (IC50 8.6x10-9 M) [40]
Description: Determined in a biochemical high-throughput mass spectrometry (HTMS) assay.
compound 8l [PMID: 36053746] Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.8 pIC50 46
⤷ pIC50 7.8 (IC50 1.5x10-8 M) [46]
oclacitinib Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 7.8 pIC50 7
⤷ pIC50 7.8 (IC50 1.75x10-8 M) [7]
rovadicitinib Small molecule or natural product Hs Inhibition >7.7 pIC50 44
⤷ pIC50 >7.7 (IC50 <2x10-8 M) [44]
Description: Binned value from patent; inhibition of WT hJAK2
pacritinib Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.6 pIC50 79
⤷ pIC50 7.6 (IC50 2.3x10-8 M) [79]
PF-06263276 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 7.6 pIC50 39
⤷ pIC50 7.6 (IC50 2.31x10-8 M) [39]
JAK inhibitor 20a Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 7.5 pIC50 23
⤷ pIC50 7.5 (IC50 2.96x10-8 M) [23]
WXFL10203614 Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 7.0 – 8.0 pIC50 84
⤷ pIC50 7.0 – 8.0 (IC50 1x10-7 – 1x10-8 M) [84]
zotiraciclib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.1 – 7.7 pIC50 29,80
⤷ pIC50 7.1 – 7.7 (IC50 7.3x10-8 – 1.9x10-8 M) [29,80]
CEE321 Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 7.3 pIC50 68
⤷ pIC50 7.3 (IC50 4.8x10-8 M) [68]
RGB-286638 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.3 pIC50 16
⤷ pIC50 7.3 (IC50 5x10-8 M) [16]
gusacitinib Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition >7.3 pIC50 73
⤷ pIC50 >7.3 (IC50 <5x10-8 M) [73]
solcitinib Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 7.2 pIC50 11
⤷ pIC50 7.2 (IC50 6.7x10-8 M) [11]
ropsacitinib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 7.1 pIC50 28
⤷ pIC50 7.1 (IC50 7.4x10-8 M) [28]
tofacitinib Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 7.1 pIC50 17
⤷ pIC50 7.1 (IC50 7.7x10-8 M) [17]
Description: In a biochemical enzyme assay.
brepocitinib Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 7.1 pIC50 24
⤷ pIC50 7.1 (IC50 7.7x10-8 M) [24]
itacitinib Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition <7.0 pIC50 35
⤷ pIC50 <7.0 (IC50 >1x10-7 M) [35]
emzeltrectinib Small molecule or natural product Click here for species-specific activity table Hs Inhibition <7.0 pIC50 43
⤷ pIC50 <7.0 (IC50 >1x10-7 M) [43]
JNJ-7706621 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.0 pIC50 58
⤷ pIC50 7.0 (IC50 1.06x10-7 M) [58]
Description: Binding to the JH2 pseudo kinase domain of JAK2 was determined using isothermal titration calorimetry (ITC).
upadacitinib Small molecule or natural product Approved drug Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 6.9 pIC50 74
⤷ pIC50 6.9 (IC50 1.2x10-7 M) [74]
decernotinib Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 6.2 – 7.6 pIC50 17
⤷ pIC50 7.6 (IC50 2.4x10-8 M) [17]
pIC50 6.2 (IC50 6.19x10-7 M) [17]
zemprocitinib Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 6.8 pIC50 76
⤷ pIC50 6.8 (IC50 1.413x10-7 M) [76]
TYK2 inhibitor 14l Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 6.8 pIC50 88
⤷ pIC50 6.8 (IC50 1.57x10-7 M) [88]
filgotinib Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 5.6 – 7.5 pIC50 17,71
⤷ pIC50 7.5 (IC50 2.8x10-8 M) [71]
pIC50 5.6 (IC50 2.4x10-6 M) [17]
girocitinib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.0 – 7.0 pIC50 45
⤷ pIC50 6.0 – 7.0 (IC50 1x10-6 – 1x10-7 M) [45]
safimaltib Small molecule or natural product Click here for species-specific activity table Hs Inhibition 6.0 – 6.5 pIC50 42
⤷ pIC50 6.0 – 6.5 (IC50 1x10-6 – 3x10-7 M) [42]
abrocitinib Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 6.1 pIC50 72
⤷ pIC50 6.1 (IC50 8.03x10-7 M) [72]
SAR-20347 Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 6.1 pIC50 82
⤷ pIC50 6.1 (IC50 8.82x10-7 M) [82]
Description: In a TR-FRET assay.
itacnosertib Small molecule or natural product Click here for species-specific activity table Hs Inhibition <6.0 pIC50 53
⤷ pIC50 <6.0 (IC50 >1x10-6 M) [53]
Description: Inhibitory activity against human JAK2 kinase, determined using a Z'-Lyte® biochemical assay.
londamocitinib Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 5.9 pIC50 55
⤷ pIC50 5.9 (IC50 1.22x10-6 M) [55]
JAK3 inhibitor 32 Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 5.5 pIC50 12
⤷ pIC50 5.5 (IC50 3.012x10-6 M) [12]
JAK3 inhibitor 34 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition <5.2 pIC50 12
⤷ pIC50 <5.2 (IC50 >6.578x10-6 M) [12]
JAK3 inhibitor II Small molecule or natural product Click here for species-specific activity table Hs Inhibition <5.0 pIC50 14
⤷ pIC50 <5.0 (IC50 >1x10-5 M) [14]
GSK2646264 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition 5.0 pIC50 5
⤷ pIC50 5.0 (IC50 1x10-5 M) [5]
golidocitinib Small molecule or natural product Click here for species-specific activity table Hs Inhibition <4.8 pIC50 65
⤷ pIC50 <4.8 (IC50 >1.5x10-5 M) [65]
Description: Inhbition of JAK2 enzymatic activity.
AC430 Small molecule or natural product Immunopharmacology Ligand Hs Inhibition - - 33
⤷ [33]
deuruxolitinib Small molecule or natural product Primary target of this compound Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition - - 75
⤷ [75]
Inhibitor Comments
Pacritinib inhibits JAK2V617F mutant with an IC50 of 19nM [79].
Other Binding Ligands
Key to terms and symbols Click column headers to sort
Ligand Sp. Action Value Parameter Reference
SJ988497 Small molecule or natural product Click here for species-specific activity table Hs Binding 9.5 pKd 13
⤷ pKd 9.5 (Kd 3.4x10-10 M) [13]
DiscoveRx KINOMEscan® screen Click here for help
A screen of 72 inhibitors against 456 human kinases. Quantitative data were derived using DiscoveRx KINOMEscan® platform.
http://www.discoverx.com/services/drug-discovery-development-services/kinase-profiling/kinomescan
Reference: 19,81
Key to terms and symbols Click column headers to sort
Target used in screen: JAK2(JH1domain-catalytic)
Ligand Sp. Type Action Value Parameter
ruxolitinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 10.4 pKd
tofacitinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 9.2 pKd
fedratinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 9.0 pKd
tamatinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 8.5 pKd
lestaurtinib Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 8.4 pKd
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 8.0 pKd
JNJ-28312141 Small molecule or natural product Hs Inhibitor Inhibition 8.0 pKd
PP-242 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 8.0 pKd
NVP-TAE684 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.8 pKd
KW-2449 Small molecule or natural product Hs Inhibitor Inhibition 7.1 pKd
Displaying the top 10 most potent ligands  View all ligands in screen »
EMD Millipore KinaseProfilerTM screen/Reaction Biology Kinase HotspotSM screen Click here for help
A screen profiling 158 kinase inhibitors (Calbiochem Protein Kinase Inhibitor Library I and II, catalogue numbers 539744 and 539745) for their inhibitory activity at 1µM and 10µM against 234 human recombinant kinases using the EMD Millipore KinaseProfilerTM service.

A screen profiling the inhibitory activity of 178 commercially available kinase inhibitors at 0.5µM against a panel of 300 recombinant protein kinases using the Reaction Biology Corporation Kinase HotspotSM platform.

http://www.millipore.com/techpublications/tech1/pf3036
http://www.reactionbiology.com/webapps/main/pages/kinase.aspx

Reference: 1,27
Key to terms and symbols Click column headers to sort
Target used in screen: JAK2/JAK2
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
JAK inhibitor I Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 1.4 -1.0 1.0
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 1.9 0.0 -1.5
K-252a Small molecule or natural product Hs Inhibitor Inhibition 3.0 2.0 -1.0
Cdk1/2 inhibitor III Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 3.2 2.0 0.0
Cdk2 inhibitor IV Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 4.2 3.0 -1.0
tofacitinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 5.1
Gö 6976 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 5.6 4.0 3.0
IKK-2 inhibitor IV Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 7.2 4.0 0.0
midostaurin Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 8.9 7.0 2.0
SB 218078 Small molecule or natural product Hs Inhibitor Inhibition 14.2 86.0 82.0
Displaying the top 10 most potent ligands  View all ligands in screen »
Immunopharmacology Comments
JAK2 signal transduction is a critical mediator of the immune response and is implicated in autoimmune conditions and in graft-versus-host disease (GvHD). The pro-inflammatory effects of IL-6, IL-12, and IL-23 on T cells are mediated via JAK2 [8,10,63], as is IL-12/IL-23-driven Th1 and Th17 differentiation [8,63,87]. JAK2 is an alternative intervention point that can be manipulated to reduce pathogenic Th1/Th17 responses.

Genetic deletion or pharmacologic inhibition of JAK2 (using pacritinib) concomittantly enhances beneficial Th2 and Treg differentiation and efficiently impairs alloreactive Th1 responses, a combined effect that results in reduced GvHD lethality and extends the graft-versus-leukemia effect [9]. This beneficial effect is also observed in solid organ transplant models. The ffficacy of combining pacritinib with standard immune suppression (sirolimus/tacrolimus) after allogeneic hematopoietic cell transplantation is being evaluated in Phase 1/2 clinical trial NCT02891603.

CEP-33779, a selective JAK2 inhibitor has demonstrated efficacy in mouse models of rheumatoid arthritis [64] and colitis-induced colorectal cancer [62].
Immuno Process Associations
Immuno Process:  Inflammation
Immuno Process:  Immune regulation
Immuno Process:  Immune system development
Immuno Process:  Cytokine production & signalling
Immuno Process:  T cell (activation)
Immuno Process:  B cell (activation)
Immuno Process:  Cellular signalling
Immuno Disease Associations
Disease Name:  Myelofibrosis
Disease Synonyms:  no synonynms
Comment:  Somatic mutations in the JAK2 gene have been identified in many cases of myelofibrosis.
Disease X-refs:  Disease Ontology: DOID:4971
OMIM: 254450
Orphanet: ORPHA824
References:  6,41
Disease Name:  Polycythemia vera
Disease Synonyms:  no synonynms
Comment:  Most cases of PV are associated with a somatic mutation in the JAK2 gene. The JAK2 V617F mutation causes constitutive tyrosine phosphorylation activity which promotes phenotypic changes consistent with PV pathology.
Disease X-refs:  Disease Ontology: DOID:8997
OMIM: 263300
Orphanet: ORPHA729
References:  6,38,41
Clinically-Relevant Mutations and Pathophysiology Click here for help
Disease:  Acute myeloid leukemia
Synonyms: Acute myelogenous leukemia
Disease Ontology: DOID:9119
OMIM: 601626
Orphanet: ORPHA519
Disease:  Budd-Chiari syndrome
OMIM: 600880
Orphanet: ORPHA131
Disease:  Familial thrombocytosis
Description: A rare chronic myeloproliferative neoplasm (MPN) causing overproduction of platelets.
Synonyms: essential thrombocythaemia
hemorrhagic thrombocythemia
hereditary thrombocythemia
primary thrombocytosis
Disease Ontology: DOID:2224
Orphanet: ORPHA71493
Disease:  Myelofibrosis
Synonyms: Myelofibrosis with myeloid metaplasia [Orphanet: ORPHA824]
Disease Ontology: DOID:4971
OMIM: 254450
Orphanet: ORPHA824
Disease:  Polycythemia vera
Disease Ontology: DOID:8997
OMIM: 263300
Orphanet: ORPHA729
Disease:  Thrombocythemia 3; THCYT3
Synonyms: Essential thrombocythemia [Orphanet: ORPHA3318]
Essential thrombocytosis [Orphanet: ORPHA3318]
OMIM: 614521
Orphanet: ORPHA3318

References

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1. Anastassiadis T, Deacon SW, Devarajan K, Ma H, Peterson JR. (2011) Comprehensive assay of kinase catalytic activity reveals features of kinase inhibitor selectivity. Nat Biotechnol, 29 (11): 1039-45. [PMID:22037377]

2. Andraos R, Qian Z, Bonenfant D, Rubert J, Vangrevelinghe E, Scheufler C, Marque F, Régnier CH, De Pover A, Ryckelynck H et al.. (2012) Modulation of activation-loop phosphorylation by JAK inhibitors is binding mode dependent. Cancer Discov, 2 (6): 512-23. [PMID:22684457]

3. Asshoff M, Petzer V, Warr MR, Haschka D, Tymoszuk P, Demetz E, Seifert M, Posch W, Nairz M, Maciejewski P et al.. (2017) Momelotinib inhibits ACVR1/ALK2, decreases hepcidin production, and ameliorates anemia of chronic disease in rodents. Blood, 129 (13): 1823-1830. [PMID:28188131]

4. Bach J, Eastwood P, González J, Gómez E, Alonso JA, Fonquerna S, Lozoya E, Orellana A, Maldonado M, Calaf E et al.. (2019) Identification of 2-Imidazopyridine and 2-Aminopyridone Purinones as Potent Pan-Janus Kinase (JAK) Inhibitors for the Inhaled Treatment of Respiratory Diseases. J Med Chem, 62 (20): 9045-9060. [PMID:31609613]

5. Barker MD, Liddle J, Atkinson FL, Wilson DM, Dickson MC, Ramirez-Molina C, Lewis H, Davis RP, Somers DO, Neu M et al.. (2018) Discovery of potent and selective Spleen Tyrosine Kinase inhibitors for the topical treatment of inflammatory skin disease. Bioorg Med Chem Lett, 28 (21): 3458-3462. [PMID:30249354]

6. Baxter EJ, Scott LM, Campbell PJ, East C, Fourouclas N, Swanton S, Vassiliou GS, Bench AJ, Boyd EM, Curtin N et al.. (2005) Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders. Lancet, 365 (9464): 1054-61. [PMID:15781101]

7. Berlinski PJ, Birchmeier MJ, Bowman JW, Gonzales AJ, Kamerling SG, Mann DW, Mitton-Fry MJ. (2010) Pyrrolo[2,3-d]pyrimidine compounds. Patent number: WO2010020905. Assignee: Pfizer Inc.. Priority date: 20/08/2008. Publication date: 25/02/2010.

8. Betts BC, Abdel-Wahab O, Curran SA, St Angelo ET, Koppikar P, Heller G, Levine RL, Young JW. (2011) Janus kinase-2 inhibition induces durable tolerance to alloantigen by human dendritic cell-stimulated T cells yet preserves immunity to recall antigen. Blood, 118 (19): 5330-9. [PMID:21917753]

9. Betts BC, Bastian D, Iamsawat S, Nguyen H, Heinrichs JL, Wu Y, Daenthanasanmak A, Veerapathran A, O'Mahony A, Walton K et al.. (2018) Targeting JAK2 reduces GVHD and xenograft rejection through regulation of T cell differentiation. Proc Natl Acad Sci USA, 115 (7): 1582-1587. [PMID:29382747]

10. Betts BC, Sagatys EM, Veerapathran A, Lloyd MC, Beato F, Lawrence HR, Yue B, Kim J, Sebti SM, Anasetti C et al.. (2015) CD4+ T cell STAT3 phosphorylation precedes acute GVHD, and subsequent Th17 tissue invasion correlates with GVHD severity and therapeutic response. J Leukoc Biol, 97 (4): 807-19. [PMID:25663681]

11. Blanc J. (2010) Novel compound useful for the treatment of degenerative and inflammatory diseases. Patent number: WO2010149771. Assignee: Galapagos Nv, Menet, Christel Jeanne Marie. Priority date: 26/06/2009. Publication date: 29/12/2010.

12. Casimiro-Garcia A, Trujillo JI, Vajdos F, Juba B, Banker ME, Aulabaugh A, Balbo P, Bauman J, Chrencik J, Coe JW et al.. (2018) Identification of Cyanamide-Based Janus Kinase 3 (JAK3) Covalent Inhibitors. J Med Chem, 61 (23): 10665-10699. [PMID:30423248]

13. Chang Y, Min J, Jarusiewicz JA, Actis M, Yu-Chen Bradford S, Mayasundari A, Yang L, Chepyala D, Alcock LJ, Roberts KG et al.. (2021) Degradation of Janus kinases in CRLF2-rearranged acute lymphoblastic leukemia. Blood, 138 (23): 2313-2326. [PMID:34110416]

14. Changelian PS, Moshinsky D, Kuhn CF, Flanagan ME, Munchhof MJ, Harris TM, Whipple DA, Doty JL, Sun J, Kent CR et al.. (2008) The specificity of JAK3 kinase inhibitors. Blood, 111 (4): 2155-7. [PMID:18094329]

15. Chen H, Chan BK, Drummond J, Estrada AA, Gunzner-Toste J, Liu X, Liu Y, Moffat J, Shore D, Sweeney ZK et al.. (2012) Discovery of selective LRRK2 inhibitors guided by computational analysis and molecular modeling. J Med Chem, 55 (11): 5536-45. [PMID:22591441]

16. Cirstea D, Hideshima T, Santo L, Eda H, Mishima Y, Nemani N, Hu Y, Mimura N, Cottini F, Gorgun G et al.. (2013) Small-molecule multi-targeted kinase inhibitor RGB-286638 triggers P53-dependent and -independent anti-multiple myeloma activity through inhibition of transcriptional CDKs. Leukemia, 27 (12): 2366-75. [PMID:23807770]

17. Clark JD, Flanagan ME, Telliez JB. (2014) Discovery and development of Janus kinase (JAK) inhibitors for inflammatory diseases. J Med Chem, 57 (12): 5023-38. [PMID:24417533]

18. Coffey G, Betz A, DeGuzman F, Pak Y, Inagaki M, Baker DC, Hollenbach SJ, Pandey A, Sinha U. (2014) The novel kinase inhibitor PRT062070 (Cerdulatinib) demonstrates efficacy in models of autoimmunity and B-cell cancer. J Pharmacol Exp Ther, 351 (3): 538-48. [PMID:25253883]

19. Davis MI, Hunt JP, Herrgard S, Ciceri P, Wodicka LM, Pallares G, Hocker M, Treiber DK, Zarrinkar PP. (2011) Comprehensive analysis of kinase inhibitor selectivity. Nat Biotechnol, 29 (11): 1046-51. [PMID:22037378]

20. Dengler HS, Wu X, Peng I, Rinderknecht CH, Kwon Y, Suto E, Kohli PB, Liimatta M, Barrett K, Lloyd J et al.. (2018) Lung-restricted inhibition of Janus kinase 1 is effective in rodent models of asthma. Sci Transl Med, 10 (468): eaao2151. [PMID:30463918]

21. Drilon A, Ou SI, Cho BC, Kim DW, Lee J, Lin JJ, Zhu VW, Ahn MJ, Camidge DR, Nguyen J et al.. (2018) Repotrectinib (TPX-0005) Is a Next-Generation ROS1/TRK/ALK Inhibitor That Potently Inhibits ROS1/TRK/ALK Solvent- Front Mutations. Cancer Discov, 8 (10): 1227-1236. [PMID:30093503]

22. Dugan BJ, Gingrich DE, Mesaros EF, Milkiewicz KL, Curry MA, Zulli AL, Dobrzanski P, Serdikoff C, Jan M, Angeles TS et al.. (2012) A selective, orally bioavailable 1,2,4-triazolo[1,5-a]pyridine-based inhibitor of Janus kinase 2 for use in anticancer therapy: discovery of CEP-33779. J Med Chem, 55 (11): 5243-54. [PMID:22594690]

23. Elsayed MSA, Nielsen JJ, Park S, Park J, Liu Q, Kim CH, Pommier Y, Agama K, Low PS, Cushman M. (2018) Application of Sequential Palladium Catalysis for the Discovery of Janus Kinase Inhibitors in the Benzo[ c]pyrrolo[2,3- h][1,6]naphthyridin-5-one (BPN) Series. J Med Chem, 61 (23): 10440-10462. [PMID:30460842]

24. Fensome A, Ambler CM, Arnold E, Banker ME, Brown MF, Chrencik J, Clark JD, Dowty ME, Efremov IV, Flick A et al.. (2018) Dual Inhibition of TYK2 and JAK1 for the Treatment of Autoimmune Diseases: Discovery of (( S)-2,2-Difluorocyclopropyl)((1 R,5 S)-3-(2-((1-methyl-1 H-pyrazol-4-yl)amino)pyrimidin-4-yl)-3,8-diazabicyclo[3.2.1]octan-8-yl)methanone (PF-06700841). J Med Chem, 61 (19): 8597-8612. [PMID:30113844]

25. Forsyth T, Kearney PC, Kim BG, Johnson HW, Aay N, Arcalas A, Brown DS, Chan V, Chen J, Du H et al.. (2012) SAR and in vivo evaluation of 4-aryl-2-aminoalkylpyrimidines as potent and selective Janus kinase 2 (JAK2) inhibitors. Bioorg Med Chem Lett, 22 (24): 7653-8. [PMID:23127890]

26. Fridman JS, Scherle PA, Collins R, Burn TC, Li Y, Li J, Covington MB, Thomas B, Collier P, Favata MF et al.. (2010) Selective inhibition of JAK1 and JAK2 is efficacious in rodent models of arthritis: preclinical characterization of INCB028050. J Immunol, 184 (9): 5298-307. [PMID:20363976]

27. Gao Y, Davies SP, Augustin M, Woodward A, Patel UA, Kovelman R, Harvey KJ. (2013) A broad activity screen in support of a chemogenomic map for kinase signalling research and drug discovery. Biochem J, 451 (2): 313-28. [PMID:23398362]

28. Gerstenberger BS, Ambler C, Arnold EP, Banker ME, Brown MF, Clark JD, Dermenci A, Dowty ME, Fensome A, Fish S et al.. (2020) Discovery of Tyrosine Kinase 2 (TYK2) Inhibitor (PF-06826647) for the Treatment of Autoimmune Diseases. J Med Chem, 63 (22): 13561-13577. [PMID:32787094]

29. Goh KC, Novotny-Diermayr V, Hart S, Ong LC, Loh YK, Cheong A, Tan YC, Hu C, Jayaraman R, William AD et al.. (2012) TG02, a novel oral multi-kinase inhibitor of CDKs, JAK2 and FLT3 with potent anti-leukemic properties. Leukemia, 26 (2): 236-43. [PMID:21860433]

30. Gozgit JM, Bebernitz G, Patil P, Ye M, Parmentier J, Wu J, Su N, Wang T, Ioannidis S, Davies A et al.. (2008) Effects of the JAK2 inhibitor, AZ960, on Pim/BAD/BCL-xL survival signaling in the human JAK2 V617F cell line SET-2. J Biol Chem, 283 (47): 32334-43. [PMID:18775810]

31. Hanan EJ, Liang J, Wang X, Blake RA, Blaquiere N, Staben ST. (2020) Monomeric Targeted Protein Degraders. J Med Chem, 63 (20): 11330-11361. [PMID:32352776]

32. Hanan EJ, van Abbema A, Barrett K, Blair WS, Blaney J, Chang C, Eigenbrot C, Flynn S, Gibbons P, Hurley CA et al.. (2012) Discovery of potent and selective pyrazolopyrimidine janus kinase 2 inhibitors. J Med Chem, 55 (22): 10090-107. [PMID:23061660]

33. Holladay MW, Setti E. (2014) Optically active pyrazolylaminoquinazoline, and pharmaceutical compositions and methods of use thereof. Patent number: US8703943. Assignee: Ambit Biosciences Corporation. Priority date: 01/09/2010. Publication date: 22/04/2014.

34. Howard S, Berdini V, Boulstridge JA, Carr MG, Cross DM, Curry J, Devine LA, Early TR, Fazal L, Gill AL et al.. (2009) Fragment-based discovery of the pyrazol-4-yl urea (AT9283), a multitargeted kinase inhibitor with potent aurora kinase activity. J Med Chem, 52 (2): 379-88. [PMID:19143567]

35. Huang T, Xue C-B, Wang A, Kong L, Ye HF, Yao W, Rodgers JD, Shepard S, Wang H, Shao L et al.. (2011) Piperidin-4-yl azetidine derivatives as jak1 inhibitors. Patent number: WO2011112662. Assignee: Incyte Corporation. Priority date: 10/03/2010. Publication date: 15/09/2011.

36. Hudson R, Kozak J, Fatheree PR, Podesto DD, Brandt GEL, Fleury M, Beausoleil A-M, Huang X, Thalladi VR. (2016) Naphthyridine compounds as jak kinase inhibitors. Patent number: WO2016191524A1. Assignee: Theravance Biopharma R&D. Priority date: 28/05/2015. Publication date: 01/12/2016.

37. Ito M, Yamazaki S, Yamagami K, Kuno M, Morita Y, Okuma K, Nakamura K, Chida N, Inami M, Inoue T et al.. (2017) A novel JAK inhibitor, peficitinib, demonstrates potent efficacy in a rat adjuvant-induced arthritis model. J Pharmacol Sci, 133 (1): 25-33. [PMID:28117214]

38. James C, Ugo V, Le Couédic JP, Staerk J, Delhommeau F, Lacout C, Garçon L, Raslova H, Berger R, Bennaceur-Griscelli A et al.. (2005) A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera. Nature, 434 (7037): 1144-8. [PMID:15793561]

39. Jones P, Storer RI, Sabnis YA, Wakenhut FM, Whitlock GA, England KS, Mukaiyama T, Dehnhardt CM, Coe JW, Kortum SW et al.. (2017) Design and Synthesis of a Pan-Janus Kinase Inhibitor Clinical Candidate (PF-06263276) Suitable for Inhaled and Topical Delivery for the Treatment of Inflammatory Diseases of the Lungs and Skin. J Med Chem, 60 (2): 767-786. [PMID:27983835]

40. Koudriakova T, Kreutter K, Leonard K, Rizzolio M, Smith RC, Tichenor MS, Wang A. (2018) Small molecule inhibitors of the JAK family of kinases. Patent number: WO2018112379A1. Assignee: Janssen Pharmaceutica. Priority date: 16/12/2016. Publication date: 21/06/2018.

41. Kralovics R, Passamonti F, Buser AS, Teo SS, Tiedt R, Passweg JR, Tichelli A, Cazzola M, Skoda RC. (2005) A gain-of-function mutation of JAK2 in myeloproliferative disorders. N Engl J Med, 352 (17): 1779-90. [PMID:15858187]

42. Li Y-L, Zhuo J, Qian D-Q, Mei S, Cao G, Pan Y, Li Q, Jia Z. (2021) Bipyrazole derivatives as jak inhibitors. Patent number: US20210238168A1. Assignee: Incyte Corp. Priority date: 17/05/2013. Publication date: 05/08/2021.

43. Li Z, Hu Y, Wei W, Liguang D, Xiaowei D, Yanqing Y, Yinghui S, Yongxin H, Yong P, Fansheng K. (2018) Amino pyrazolopyrimidine compound used as neurotrophic factor tyrosine kinase receptor inhibitor. Patent number: WO2018077246A1. Assignee: Chia Tai Tianqing Pharmaceutical Group Co., Ltd., Beijing Sailintai Pharmaceutical Technology Co., Ltd., Lianyungang Runzhong Pharmaceutical Co., Ltd.. Priority date: 27/10/2017. Publication date: 03/05/2018.

44. Li Z, Xiao D, Hu Y, Dai L, Duan X, Sun Y, Peng Y, Kong F, Luo H, Han Y et al.. (2022) Pyrrolopyrimidine compound. Patent number: US10561657B2. Assignee: Centaurus Biopharma Co Ltd Chia Tai Tianqing Pharmaceutical Group Co Ltd Lianyungang Runzhong Pharmaceutical Co Ltd. Priority date: 16/12/2014. Publication date: 18/02/2022.

45. Liang C. (2020) JAK1 selective inhibitors and uses thereof. Patent number: US10738060B2. Assignee: Hangzhou Highlightll Pharmaceutical Co Ltd, Tll Pharmaceutical LLC. Priority date: 30/09/2017. Publication date: 11/08/2020.

46. Liang X, Xie Y, Liu X, Xu H, Ren H, Tang S, Liu Q, Huang M, Shao X, Li C et al.. (2022) Discovery of Novel Imidazo[4,5-c]quinoline Derivatives to Treat Inflammatory Bowel Disease (IBD) by Inhibiting Multiple Proinflammatory Signaling Pathways and Restoring Intestinal Homeostasis. J Med Chem, 65 (18): 11949-11969. [PMID:36053746]

47. Liosi ME, Ippolito JA, Henry SP, Krimmer SG, Newton AS, Cutrona KJ, Olivarez RA, Mohanty J, Schlessinger J, Jorgensen WL. (2022) Insights on JAK2 Modulation by Potent, Selective, and Cell-Permeable Pseudokinase-Domain Ligands. J Med Chem, 65 (12): 8380-8400. [PMID:35653642]

48. Long DD, Smith C, Thompson C. (2020) DIMETHYL AMINO AZETIDINE AMIDES AS JAK INHIBITORS. Patent number: WO/2020/051105. Assignee: THERAVANCE BIOPHARMA. Priority date: 04/09/2018. Publication date: 12/03/2020.

49. Lucet IS, Fantino E, Styles M, Bamert R, Patel O, Broughton SE, Walter M, Burns CJ, Treutlein H, Wilks AF et al.. (2006) The structural basis of Janus kinase 2 inhibition by a potent and specific pan-Janus kinase inhibitor. Blood, 107 (1): 176-83. [PMID:16174768]

50. Ma B, Bohnert T, Otipoby KL, Tien E, Arefayene M, Bai J, Bajrami B, Bame E, Chan TR, Humora M et al.. (2020) Discovery of BIIB068: A Selective, Potent, Reversible Bruton's Tyrosine Kinase Inhibitor as an Orally Efficacious Agent for Autoimmune Diseases. J Med Chem, 63 (21): 12526-12541. [PMID:32696648]

51. Ma L, Clayton JR, Walgren RA, Zhao B, Evans RJ, Smith MC, Heinz-Taheny KM, Kreklau EL, Bloem L, Pitou C et al.. (2013) Discovery and characterization of LY2784544, a small-molecule tyrosine kinase inhibitor of JAK2V617F. Blood Cancer J, 3: e109. [PMID:23584399]

52. Malerich JP, Lam JS, Hart B, Fine RM, Klebansky B, Tanga MJ, D'Andrea A. (2010) Diamino-1,2,4-triazole derivatives are selective inhibitors of TYK2 and JAK1 over JAK2 and JAK3. Bioorg Med Chem Lett, 20 (24): 7454-7. [PMID:21106455]

53. Mollard A, Warner SL, Flymm GA, Vankayalapati H, Bearss DJ. (2014) Jak2 and alk2 inhibitors and methods for their use. Patent number: WO2014151871A9. Assignee: Tolero Pharmaceuticals, Inc.. Priority date: 14/03/2013. Publication date: 31/12/2014.

54. Nakaya Y, Shide K, Niwa T, Homan J, Sugahara S, Horio T, Kuramoto K, Kotera T, Shibayama H, Hori K et al.. (2011) Efficacy of NS-018, a potent and selective JAK2/Src inhibitor, in primary cells and mouse models of myeloproliferative neoplasms. Blood Cancer J, 1 (7): e29. [PMID:22829185]

55. Nilsson KM, Astrand ABM, Berggren AIK, Johansson JR, Lepisto MJ, Kawatkar SP, Su Q, Kettle JG. (2018) Jak1 selective inhibitors. Patent number: WO2018134213A1. Assignee: Astrazeneca Ab. Priority date: 17/01/2017. Publication date: 26/07/2018.

56. Noji S, Hara Y, Miura T, Yamanaka H, Maeda K, Hori A, Yamamoto H, Obika S, Inoue M, Hase Y et al.. (2020) Discovery of a Janus Kinase Inhibitor Bearing a Highly Three-Dimensional Spiro Scaffold: JTE-052 (Delgocitinib) as a New Dermatological Agent to Treat Inflammatory Skin Disorders. J Med Chem, 63 (13): 7163-7185. [PMID:32511913]

57. Pardanani A, Lasho T, Smith G, Burns CJ, Fantino E, Tefferi A. (2009) CYT387, a selective JAK1/JAK2 inhibitor: in vitro assessment of kinase selectivity and preclinical studies using cell lines and primary cells from polycythemia vera patients. Leukemia, 23 (8): 1441-5. [PMID:19295546]

58. Puleo DE, Kucera K, Hammarén HM, Ungureanu D, Newton AS, Silvennoinen O, Jorgensen WL, Schlessinger J. (2017) Identification and Characterization of JAK2 Pseudokinase Domain Small Molecule Binders. ACS Med Chem Lett, 8 (6): 618-621. [PMID:28626521]

59. Purandare AV, McDevitt TM, Wan H, You D, Penhallow B, Han X, Vuppugalla R, Zhang Y, Ruepp SU, Trainor GL et al.. (2012) Characterization of BMS-911543, a functionally selective small-molecule inhibitor of JAK2. Leukemia, 26 (2): 280-8. [PMID:22015772]

60. Qiu Q, Chi F, Zhou D, Xie Z, Liu Y, Wu H, Yin Z, Shi W, Qian H. (2023) Exploration of Janus Kinase (JAK) and Histone Deacetylase (HDAC) Bispecific Inhibitors Based on the Moiety of Fedratinib for Treatment of Both Hematologic Malignancies and Solid Cancers. J Med Chem, 66 (8): 5753-5773. [PMID:37057760]

61. Quintás-Cardama A, Vaddi K, Liu P, Manshouri T, Li J, Scherle PA, Caulder E, Wen X, Li Y, Waeltz P et al.. (2010) Preclinical characterization of the selective JAK1/2 inhibitor INCB018424: therapeutic implications for the treatment of myeloproliferative neoplasms. Blood, 115 (15): 3109-17. [PMID:20130243]

62. Seavey MM, Lu LD, Stump KL, Wallace NH, Hockeimer W, O'Kane TM, Ruggeri BA, Dobrzanski P. (2012) Therapeutic efficacy of CEP-33779, a novel selective JAK2 inhibitor, in a mouse model of colitis-induced colorectal cancer. Mol Cancer Ther, 11 (4): 984-93. [PMID:22334590]

63. Spoerl S, Mathew NR, Bscheider M, Schmitt-Graeff A, Chen S, Mueller T, Verbeek M, Fischer J, Otten V, Schmickl M et al.. (2014) Activity of therapeutic JAK 1/2 blockade in graft-versus-host disease. Blood, 123 (24): 3832-42. [PMID:24711661]

64. Stump KL, Lu LD, Dobrzanski P, Serdikoff C, Gingrich DE, Dugan BJ, Angeles TS, Albom MS, Ator MA, Dorsey BD et al.. (2011) A highly selective, orally active inhibitor of Janus kinase 2, CEP-33779, ablates disease in two mouse models of rheumatoid arthritis. Arthritis Res Ther, 13 (2): R68. [PMID:21510883]

65. Su Q, Banks E, Bebernitz G, Bell K, Borenstein CF, Chen H, Chuaqui CE, Deng N, Ferguson AD, Kawatkar S et al.. (2020) Discovery of (2R)-N-[3-[2-[(3-Methoxy-1-methyl-pyrazol-4-yl)amino]pyrimidin-4-yl]-1H-indol-7-yl]-2-(4-methylpiperazin-1-yl)propenamide (AZD4205) as a Potent and Selective Janus Kinase 1 Inhibitor. J Med Chem, 63 (9): 4517-4527. [PMID:32297743]

66. Su Q, Ioannidis S, Chuaqui C, Almeida L, Alimzhanov M, Bebernitz G, Bell K, Block M, Howard T, Huang S et al.. (2014) Discovery of 1-methyl-1H-imidazole derivatives as potent Jak2 inhibitors. J Med Chem, 57 (1): 144-58. [PMID:24359159]

67. Tanimoto A, Ogawa Y, Oki C, Kimoto Y, Nozawa K, Amano W, Noji S, Shiozaki M, Matsuo A, Shinozaki Y et al.. (2015) Pharmacological properties of JTE-052: a novel potent JAK inhibitor that suppresses various inflammatory responses in vitro and in vivo. Inflamm Res, 64 (1): 41-51. [PMID:25387665]

68. Thoma G, Duthaler RO, Waelchli R, Hauchard A, Bruno S, Strittmatter-Keller U, Orjuela Leon A, Viebrock S, Aichholz R, Beltz K et al.. (2023) Discovery and Characterization of the Topical Soft JAK Inhibitor CEE321 for Atopic Dermatitis. J Med Chem, 66 (3): 2161-2168. [PMID:36657024]

69. Thompson JE, Cubbon RM, Cummings RT, Wicker LS, Frankshun R, Cunningham BR, Cameron PM, Meinke PT, Liverton N, Weng Y et al.. (2002) Photochemical preparation of a pyridone containing tetracycle: a Jak protein kinase inhibitor. Bioorg Med Chem Lett, 12 (8): 1219-23. [PMID:11934592]

70. Tovar C, Higgins B, Deo D, Kolinsky K, Liu JJ, Heimbrook DC, Vassilev LT. (2010) Small-molecule inducer of cancer cell polyploidy promotes apoptosis or senescence: Implications for therapy. Cell Cycle, 9 (16): 3364-75. [PMID:20814247]

71. Van Rompaey L, Galien R, van der Aar EM, Clement-Lacroix P, Nelles L, Smets B, Lepescheux L, Christophe T, Conrath K, Vandeghinste N et al.. (2013) Preclinical characterization of GLPG0634, a selective inhibitor of JAK1, for the treatment of inflammatory diseases. J Immunol, 191 (7): 3568-77. [PMID:24006460]

72. Vazquez ML, Kaila N, Strohbach JW, Trzupek JD, Brown MF, Flanagan ME, Mitton-Fry MJ, Johnson TA, TenBrink RE, Arnold EP et al.. (2018) Identification of N-{cis-3-[Methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclobutyl}propane-1-sulfonamide (PF-04965842): A Selective JAK1 Clinical Candidate for the Treatment of Autoimmune Diseases. J Med Chem, 61 (3): 1130-1152. [PMID:29298069]

73. Venkatesan A, Smith RS, Hosahalli S, Potluri V, Panigrahi SK, Basetti V, Kuntu K. (2013) Pyrimido- pyridazinone compounds and use thereof. Patent number: WO2013028818A1. Assignee: Asana Biosciences LLC. Priority date: 23/08/2011. Publication date: 28/02/2013.

74. Voss JW, Camp HS, Padley RJ. (2015) Jak1 selective inhibitor and uses thereof. Patent number: WO2015061665. Assignee: Abbvie Inc.. Priority date: 24/10/2013. Publication date: 30/04/2015.

75. Wagner AT, Cassella JV, Graham PB, Braman V, Uttamsingh V, Von Hehn J, Hamilton CE. (2017) Treatment of hair loss disorders with deuterated jak inhibitors. Patent number: WO2017192905A1. Assignee: Concert Pharmaceuticals. Priority date: 04/05/2016. Publication date: 09/11/2017.

76. Wan Z, Vazquez ML. (2022) Tricyclic janus kinase 1 inhibitors, and compositions and methods thereof. Patent number: US20220009927. Assignee: Lynk Pharmaceuticals Co Ltd. Priority date: 01/11/2019. Publication date: 13/01/2022.

77. Wang T, Ioannidis S, Almeida L, Block MH, Davies AM, Lamb ML, Scott DA, Su M, Zhang HJ, Alimzhanov M et al.. (2011) In vitro and in vivo evaluation of 6-aminopyrazolyl-pyridine-3-carbonitriles as JAK2 kinase inhibitors. Bioorg Med Chem Lett, 21 (10): 2958-61. [PMID:21493067]

78. Wernig G, Kharas MG, Okabe R, Moore SA, Leeman DS, Cullen DE, Gozo M, McDowell EP, Levine RL, Doukas J et al.. (2008) Efficacy of TG101348, a selective JAK2 inhibitor, in treatment of a murine model of JAK2V617F-induced polycythemia vera. Cancer Cell, 13 (4): 311-20. [PMID:18394554]

79. William AD, Lee AC, Blanchard S, Poulsen A, Teo EL, Nagaraj H, Tan E, Chen D, Williams M, Sun ET et al.. (2011) Discovery of the macrocycle 11-(2-pyrrolidin-1-yl-ethoxy)-14,19-dioxa-5,7,26-triaza-tetracyclo[19.3.1.1(2,6).1(8,12)]heptacosa-1(25),2(26),3,5,8,10,12(27),16,21,23-decaene (SB1518), a potent Janus kinase 2/fms-like tyrosine kinase-3 (JAK2/FLT3) inhibitor for the treatment of myelofibrosis and lymphoma. J Med Chem, 54 (13): 4638-58. [PMID:21604762]

80. William AD, Lee AC, Goh KC, Blanchard S, Poulsen A, Teo EL, Nagaraj H, Lee CP, Wang H, Williams M et al.. (2012) Discovery of kinase spectrum selective macrocycle (16E)-14-methyl-20-oxa-5,7,14,26-tetraazatetracyclo[19.3.1.1(2,6).1(8,12)]heptacosa-1(25),2(26),3,5,8(27),9,11,16,21,23-decaene (SB1317/TG02), a potent inhibitor of cyclin dependent kinases (CDKs), Janus kinase 2 (JAK2), and fms-like tyrosine kinase-3 (FLT3) for the treatment of cancer. J Med Chem, 55 (1): 169-96. [PMID:22148278]

81. Wodicka LM, Ciceri P, Davis MI, Hunt JP, Floyd M, Salerno S, Hua XH, Ford JM, Armstrong RC, Zarrinkar PP et al.. (2010) Activation state-dependent binding of small molecule kinase inhibitors: structural insights from biochemistry. Chem Biol, 17 (11): 1241-9. [PMID:21095574]

82. Works MG, Yin F, Yin CC, Yiu Y, Shew K, Tran TT, Dunlap N, Lam J, Mitchell T, Reader J et al.. (2014) Inhibition of TYK2 and JAK1 ameliorates imiquimod-induced psoriasis-like dermatitis by inhibiting IL-22 and the IL-23/IL-17 axis. J Immunol, 193 (7): 3278-87. [PMID:25156366]

83. Wu F. (2021) Multi-kinase inhibitor compound, and crystal form and use thereof. Patent number: US10889586B2. Assignee: Nanjing Transthera Biosciences Co Ltd. Priority date: 13/12/2016. Publication date: 12/01/2021.

84. Wu H, Mao W, Huang Y, Fan L, Chen S. (2018) Janus kinase inhibitor. Patent number: US20180162879A1. Assignee: Wuxi Fortune Pharmaceutical Co Ltd. Priority date: 26/05/2016. Publication date: 14/06/2018.

85. Yang T, Hu M, Chen Y, Xiang M, Tang M, Qi W, Shi M, He J, Yuan X, Zhang C et al.. (2020) N-(Pyrimidin-2-yl)-1,2,3,4-tetrahydroisoquinolin-6-amine Derivatives as Selective Janus Kinase 2 Inhibitors for the Treatment of Myeloproliferative Neoplasms. J Med Chem, 63 (23): 14921-14936. [PMID:33256400]

86. Yang T, Hu M, Qi W, Yang Z, Tang M, He J, Chen Y, Bai P, Yuan X, Zhang C et al.. (2019) Discovery of Potent and Orally Effective Dual Janus Kinase 2/FLT3 Inhibitors for the Treatment of Acute Myelogenous Leukemia and Myeloproliferative Neoplasms. J Med Chem, 62 (22): 10305-10320. [PMID:31670517]

87. Yu Y, Wang D, Liu C, Kaosaard K, Semple K, Anasetti C, Yu XZ. (2011) Prevention of GVHD while sparing GVL effect by targeting Th1 and Th17 transcription factor T-bet and RORγt in mice. Blood, 118 (18): 5011-20. [PMID:21856864]

88. Zhang C, Qi W, Li Y, Tang M, Yang T, Liu K, Chen Y, Deng D, Xiang M, Chen L. (2021) Discovery of 3-(4-(2-((1 H-Indol-5-yl)amino)-5-fluoropyrimidin-4-yl)-1 H-pyrazol-1-yl)propanenitrile Derivatives as Selective TYK2 Inhibitors for the Treatment of Inflammatory Bowel Disease. Journal of Medicinal Chemistry,. DOI: 10.1021/acs.jmedchem.0c01468 [PMID:33593051]

89. Zhang X, Dong Q, Liu B, Zhu Y, Li X, Lan J. (2013) Pyrrole six-membered heteroaryl ring derivative, preparation method therefor, and medicinal uses thereof. Patent number: WO2013091539A1. Assignee: Jiangsu Hengrui Medicine Co., Ltd., Shanghai Hengrui Medicine Co., Ltd.. Priority date: 21/12/2011. Publication date: 27/06/2013.

90. Zhao C, Zhang Y, Zhang J, Li S, Liu M, Geng Y, Liu F, Chai Q, Meng H, Li M et al.. (2023) Discovery of Novel Fedratinib-Based HDAC/JAK/BRD4 Triple Inhibitors with Remarkable Antitumor Activity against Triple Negative Breast Cancer. J Med Chem, 66 (20): 14150-14174. [PMID:37796543]

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Janus kinase (JakA) family: Janus kinase 2. Last modified on 06/03/2024. Accessed on 18/04/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetomalariapharmacology.org/GRAC/ObjectDisplayForward?objectId=2048.